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Myeloma

Critical evaluation of ASO RQ-PCR for minimal residual disease evaluation in multiple myeloma. A comparative analysis with flow cytometry

Leukemia volume 28, pages 391–397 (2014)Cite this article

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Abstract

We have analyzed the applicability, sensitivity and prognostic value of allele-specific oligonucleotide real-time quantitative PCR (ASO RQ-PCR) as a method for minimal residual disease (MRD) assessment in patients with multiple myeloma (MM), comparing the results with those of multiparameter flow cytometry (MFC). A total of 170 patients enrolled in three consecutive Spanish trials achieving at least partial response after treatment were included. Lack of clonality detection (n=31), unsuccessful sequencing (n=17) and suboptimal ASO performance (n=51) limited the applicability of PCR to 42% of cases. MRD was finally investigated in 103 patients (including 32 previously studied) with persistent disease identified by PCR and MFC in 54% and 46% of cases, respectively. A significant correlation in MRD quantitation by both the techniques was noted (r=0.881, P<0.001), being reflective of treatment intensity. Patients with <10−4 residual tumor cells showed longer progression-free survival (PFS) compared with the rest (not reached (NR) vs 31 months, P=0.002), with similar results observed with MFC. Among complete responders (n=62), PCR discriminated two risk groups with different PFS (49 vs 26 months, P=0.001) and overall survival (NR vs 60 months, P=0.008). Thus, although less applicable than MFC, ASO RQ-PCR is a powerful technique to assess treatment efficacy and risk stratification in MM.

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Acknowledgements

We thank Alicia Antón and Rebeca Maldonado for their technical assistance. This work has been partially supported by the Grants PS09/01450 and PI12/02311 from the Spanish ‘Instituto de Salud Carlos III (ISCIII)’, the Grants RD12/0036/0069 and 0058 from ‘Red Temática de Investigación Cooperativa en Cáncer (RTICC), Spanish Ministry of Economy and Competitiveness’ and European Regional Development Fund (ERDF) ‘Una manera de hacer Europa’, Grant number HUS412A12-1 from the ‘Consejería de Educación de la Junta de Castilla y León’ and Grant GCB-120981SAN from the ‘Asociación Española Contra el Cáncer (AECC)’. NP was partially supported by a grant from the SEHH (Sociedad Española de Hematología y Hemoterapia).

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Authors and Affiliations

  1. Department of Hematology, Hospital Universitario de Salamanca,

    N Puig, M E Sarasquete, A Balanzategui, B Paiva, H García, S Fumero, C Jiménez, M Alcoceba, M C Chillón, E Sebastián, L Marín, M V Mateos, M B Vidriales, M González, J F S Miguel & R García-Sanz

  2. IBSAL, Salamanca, Spain

    N Puig, M E Sarasquete, A Balanzategui, B Paiva, H García, S Fumero, C Jiménez, M Alcoceba, M C Chillón, E Sebastián, L Marín, M V Mateos, M B Vidriales, M González, J F S Miguel & R García-Sanz

  3. IBMCC (USAL-CSIC), Salamanca, Spain

    N Puig, M E Sarasquete, A Balanzategui, B Paiva, H García, S Fumero, C Jiménez, M Alcoceba, M C Chillón, E Sebastián, L Marín, M V Mateos, M B Vidriales, M González, J F S Miguel & R García-Sanz

  4. Department of Hematology, Hospital 12 de Octubre, Madrid, Spain

    J Martínez, M A Montalbán & J J Lahuerta

  5. Department of Hematology, Hospital Germans Trias I Pujol, Badalona, Spain

    A Oriol

  6. Department of Hematology, Hospital Clínico ‘Lozano Blesa’, Zaragoza, Spain

    L Palomera

  7. Department of Hematology, Hospital Universitario La Fe and Universidad Católica ‘San Vicente Mártir’, Valencia, Spain

    J de la Rubia

  8. Department of Hematology, Hospital Clinic I Provincial, Barcelona, Spain

    J Bladé

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  1. N Puig
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Correspondence to R García-Sanz.

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Puig, N., Sarasquete, M., Balanzategui, A. et al. Critical evaluation of ASO RQ-PCR for minimal residual disease evaluation in multiple myeloma. A comparative analysis with flow cytometry. Leukemia 28, 391–397 (2014). https://doi.org/10.1038/leu.2013.217

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